Skin cancer is the most common form of cancer in the US, each year accounting for just under half of all diagnosed cancers (3.5 million diagnoses) and 12,980 deaths with annual treatment costs of at $2.5 billion. Early and accurate diagnosis of skin cancer has significant impact on patient outcomes and health care costs but remains a highly subjective skill, with existing diagnostic devices either offering limited positive predictie value or requiring highly specialized training. Mis-diagnoses results in missed skin cancers as well as large numbers of unneeded referrals to dermatologists and unnecessary biopsies. We have been developing a novel method and device for a fast and non-invasive detection of skin cancer based on measurements of the temporal dynamics of pressure-induced blood flow in the cutaneous tumors. The central hypothesis of proposed research is that the dynamics of blood flow in response to external mechanical pressure is different in cutaneous tumors as compared to benign nevi thus presenting a diagnostic opportunity. Multiple studies have shown that skin cancer is significantly more vascularized than normal skin or benign nevi while the morphology of tumor vascular network is highly irregular contributing to changes in vascular resistance to blood flow and highly elevated interstitial fluid pressure. The proposed method relies on measuring the spatially and temporally resolved light absorption in the cutaneous tumor tissue using an optical probe which also acts as pressure application device. The method enables to characterize both the amount of blood displaced under pressure and the dynamics of blood displacement and refill. Our preliminary data from a pilot clinical study show that both the volume and the rate of the pressure-induced blood flow are significantly higher in cutaneous cancer than in benign nevi. Here we propose (1) to design and build more advanced devices to perform more detailed investigation of pressure-induced dynamics in basal and squamous cell carcinoma, and melanoma tumors; (2) to investigate instrument- and physiology-dependent factors that affect pressure-induced hemodynamics in tumor tissue and to improve our data analysis algorithms in order to optimize sensitivity and specificity of our device; and (3) to develop and test next generation optimized skin cancer detector. The long-term goal of the project is to develop a simple-to-use and low-cost non-invasive skin cancer diagnostic method and device that will (1) facilitate sensitive, specific and non-subjective assessment of suspect skin regions by general practice clinicians and nurse practitioners, (2) enable precise targeting of patients for biopsies and/or escalation of care and (3) provide overall reduction in skin cancer treatment costs.